European Commission Approves Ubeslo and Evlarco, First Global Regulatory Nod for CETP Inhibitor Obicetrapib
核心洞察
The European Commission granted marketing authorization for Ubeslo (搜索) (obicetrapib 10 mg monotherapy) and Evlarco (搜索) (obicetrapib 10 mg plus ezetimibe 10 mg) for primary hypercholesterolaemia (搜索) and mixed dyslipidaemia (搜索).
The decision marks the first regulatory approval of obicetrapib worldwide and followed a positive CHMP opinion, with Menarini holding exclusive European commercialization rights.
Phase 3 BROADWAY, BROOKLYN and TANDEM data showed LDL-C reductions of up to 40% with monotherapy and about 50% with the combination versus placebo, with tolerability comparable to placebo.
The European Commission has granted marketing authorization for Ubeslo (搜索) (obicetrapib 10 mg monotherapy) and Evlarco (搜索) (10 mg obicetrapib plus 10 mg ezetimibe fixed-dose combination) for adults with primary hypercholesterolaemia (搜索), both heterozygous familial (HeFH) and non-familial, or mixed dyslipidaemia (搜索). The decision, announced by NewAmsterdam Pharma (搜索) and its European partner Menarini Group (搜索), is the first regulatory approval of obicetrapib anywhere in the world.
The approval covers patients whose elevated low-density lipoprotein cholesterol (LDL-C) remains difficult to manage with currently available treatments. It follows a positive opinion from the European Medicines Agency (搜索)'s Committee for Medicinal Products for Human Use (CHMP).
"The European Commission approval of Ubeslo (搜索) and Evlarco (搜索) marks a major milestone for NewAmsterdam as the first regulatory approval of obicetrapib globally, a novel oral therapy, and validates years of work focused on delivering a potential new treatment option for patients who continue to struggle to achieve recommended LDL-C levels despite previously available therapies," said Michael Davidson, M.D., Chief Executive Officer of NewAmsterdam Pharma (搜索).
Phase 3 Evidence Base
The authorization is supported by data from NewAmsterdam's clinical development program, including the Phase 3 BROADWAY, BROOKLYN and TANDEM trials. In these studies, obicetrapib monotherapy produced statistically significant LDL-C reductions of up to 40% versus placebo, while the fixed-dose combination of obicetrapib and ezetimibe achieved reductions of approximately 50% versus placebo. The companies reported a tolerability profile comparable to placebo.
Obicetrapib is described as a novel, oral, low-dose CETP (搜索) inhibitor developed to overcome the limitations of current LDL-lowering treatments. Across the company's Phase 2 trials, ROSE2, TULIP, ROSE and OCEAN, as well as the Phase 3 BROOKLYN, BROADWAY and TANDEM trials, NewAmsterdam observed statistically significant LDL-lowering combined with a side effect profile similar to placebo, whether the drug was given as monotherapy or in combination.
Ongoing Outcomes and Late-Stage Programs
NewAmsterdam and Menarini continue to advance obicetrapib through multiple ongoing Phase 3 trials, including PREVAIL, a cardiovascular outcomes trial, as well as REMBRANDT and RUBENS. PREVAIL was initiated in March 2022 and is designed to assess the potential of obicetrapib to reduce occurrences of Major Adverse Cardiovascular Events (MACE). Enrollment was completed in April 2024, with more than 9,500 patients randomized.
Commercial Terms and Unmet Need
Under the licensing agreement between the two companies, Menarini holds exclusive commercialization rights for obicetrapib in Europe and is responsible for regulatory interactions and commercialization activities across the region. NewAmsterdam is entitled to tiered double-digit percentage royalties ranging from the low double-digits to the mid-twenties on net sales in the Menarini territory, plus up to an additional €833 million upon achievement of various clinical, regulatory and commercial milestones.
"This approval represents an important advancement for patients across Europe who require additional LDL-C lowering despite available therapies," said Elcin Barker Ergun, Chief Executive Officer of Menarini Group (搜索). "We are proud to reach this significant achievement alongside NewAmsterdam and look forward to leveraging our well-established commercial capabilities and deep cardiovascular expertise to bring Ubeslo (搜索) and Evlarco (搜索) to healthcare providers and eligible patients throughout Europe."
Cardiovascular disease (搜索) remains the leading cause of death globally despite the availability of lipid-lowering therapies. NewAmsterdam cites projections that by 2050 more than 184 million U.S. adults will be affected by CVD and hypertension, including 27 million with coronary heart disease and 19 million with stroke. In the United States from 2019 through 2022, CVD age-adjusted mortality rates increased by 9%, reversing the trend observed since 2010.
LDL-C target attainment remains low even with high-intensity statins and non-statin lipid-lowering therapies. According to the company, 269 million lipid-lowering prescriptions were written over the last 12 months, yet 30 million under-treated U.S. adults are not at their risk-based LDL-C goal, of which 13 million have atherosclerotic cardiovascular disease (搜索) (ASCVD). Fewer than 1 in 4 patients with ASCVD achieve an LDL-C goal below 70 mg/dL, and only 10% of very high risk ASCVD patients reach the goal below 55 mg/dL. A further 10 million patients diagnosed with elevated LDL-C are not taking any lipid-lowering therapy, including statins.
Full details on approved indications, contraindications, warnings and precautions are to be published in the Summary of Product Characteristics on the European Medicines Agency (搜索) website.